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ABSTRACT Background: Carbapenem-resistance in healthcare-associated infections (HCAIs) is of great concern, and it is urgent to improve surveillance. We aimed to describe and analyze HCAIs trends on Gram-negative antimicrobial susceptibility in a city from a developing country, following the implementation of an active surveillance program. Methods: This is an aggregated study describing data from 24 hospitals with intensive care units, including a trend analysis by Joinpoint regression between January 2012 and December 2017. Results: There were 23,578 pathogens in 39,832 HCAIs, from which 16,225 were Gram-negatives (68.8%). Carbapenem susceptibility was lowest in A. baumannii (15.4–25.9%), K. pneumoniae (51.0–55.9%), and P. aeruginosa (64.9–84.1%) and highest in E. coli (96.5–99.2%). Only K. pneumoniae showed a significant Joinpoint at 95% confidence interval: −10.71% (−18.02; −2.75) from 2012 to 2014, p = 0.02, and 6.54% (−2.00; 15.83) from 2015 to 2017, p = 0.12, which was most influenced by urinary tract infections: −9.98% (−16.02; −3.48) from 2012 to 2014, p = 0.01, and 9.66% (−1.75; 22.39) from 2015 to 2017, p = 0.09. Conclusion: Although we found a significant change toward an improvement in carbapenem susceptibility in K. pneumoniae, resistance is high for most pathogens. These data should encourage health institutions to improve their prevention and control strategies.

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ABSTRACT In response to the Zika epidemics in Brazil, the ZDC molecular assay (Bio-Manguinhos) was developed and registered at the Brazilian Regulatory Agency of Health Surveillance - ANVISA. The circulation of Zika (ZIKV) Dengue (DENV) and Chikungunya (CHIKV) viruses and their clinical similarities are challenges to correctly diagnose these viruses. The simultaneous detection of ZIKV, DENV and CHIKV is an important tool for diagnosis and surveillance. Here, we present the analytical and clinical performance evaluation of ZDC molecular assay (Bio-Manguinhos) at the public health laboratories three years after its registration at ANVISA. The clinical performance demonstrates the ZDC molecular assay (Bio-Manguinhos) has 100% sensitivity and 100% specificity to detect and discriminate ZIKV, CHIKV, and DENV from clinical plasma samples. The ZDC molecular assay (Bio-Manguinhos) results were highly reproducible and no cross-reactivity was seen during testing with a panel of other infectious agents. In conclusion, the ZDC molecular assay (Bio-Manguinhos) is an accurate and reliable tool to monitor Zika, dengue and chikungunya infections in countries like Brazil with simultaneous circulation of the three viruses.

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ABSTRACT Strongyloidiasis is a helminthiasis of neglected condition that has no gold standard parasitological diagnosis due to the intermittent release of larvae in feces. This study aimed to use an scFv (single chain variable fragment) obtained by Phage Display, previously validated to detect immune complexes in serum samples from individuals infected with Strongyloides stercoralis by enzyme-linked immunosorbent assay (ELISA). Now the ability of scFv to detect the immune complexes was verified by immunofluorescence, flow cytometry using magnetic beads and surface plasmon resonance (SPR). As ELISA, the SPR, immunofluorescence and flow cytometry demonstrated the ability of scFv to detect immune complexes in sera from individuals with strongyloidiasis and discriminate them from sera of individuals with other parasitic diseases and healthy individuals. Besides de conventional ELISA, the novel approaches can also be promptly applied as auxiliary diagnostic tools to the existing parasitological method for accurate diagnosis of human strongyloidiasis.

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ABSTRACT Introduction: Hepatitis C virus (HCV) infection continues to be an important public health problem worldwide. Despite the availability of drugs that promote the cure of infection in more than 95% of cases, the identification of HCV carriers remains a major challenge. Objective: To evaluate a strategy for identifying HCV carriers based on combined criteria: screening in emergency units and specialty outpatient clinics of a tertiary hospital and among older adults (≥45 years), both suggested as efficient in epidemiological studies. Methods: A cross-sectional, analytical and descriptive study was conducted on individuals of both sexes, aged 45 years and older, attending the emergency department and specialty outpatient clinics of a University Hospital in São Paulo, Brazil, from January 2016 to June 2018. After giving formal consent, the patients were submitted to a standardized interview and rapid testing for the identification of HCV antibodies (SD BIOLINE® anti-HCV). Results: A total of 606 adult patients (62% women and 37% men) were evaluated. The mean age was 62 ± 10 years. Four positive tests were identified, with confirmation by conventional serology and HCV-RNA determination. Thus, the prevalence of HCV identified in the sample was 0.66%. All patients had a history of risk factors for infection. Conclusion: The strategies of birth-cohort testing and screening in emergency medical services for the identification of HCV carries, both suggested in the literature as efficient for the diagnosis of hepatitis C, resulted in a low rate of HCV infection. These findings highlight the magnitude of the challenge of identifying asymptomatic HCV carriers in Brazil.

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ABSTRACT Objectives: To evaluate the effectiveness of Topical Oxygen Jet Therapy (TOJT) in the treatment of surgical wounds in adult patients who has clinical signs of infection for over 30 days; and to identify the pathogens causing complicated skin and soft tissue infections. Method: Parallel, randomized clinical trials randomly divided into “Control Group” (CG) and “Treatment Group” (TG), which were followed up for 10 consecutive days. Venous antibiotics and dressings were used in both groups. In addition, TOJT were used on the wounds in the TG. The outcome criteria were based on clinical indicators: Pressure Ulcer Scale for Healing (PUSH) and Visual Analog Scale Pain (VAS). The paired t-test or Wilcoxon, chi-squared or Fisher’s exact test, and Student’s t-test or Mann–Whitney tests were used with a significance level of 5%. Results: 73 inpatients were included and followed up: 39 in TG and 34, CG. There were no significant differences in socio-demographic variables or of initial laboratory tests, except for blood glucose that was higher in TG than in CG (p = 0.044). Ten days into treatment, both the area of PUSH wounds (p < 0.001) and the pain scale (p = 0.029) were significantly reduced in TG. Staphylococcus aureus was the most prevalent pathogen (40%) with no significant difference between the two groups. Discussion: Although the follow-up time was of only ten days, a significant improvement was observed in TG. As a limitation of the study, the small sample size precluded the comparison of S. aureus infections between the two groups. Conclusion: TOJT accelerated the healing process, reduced pain and contributed to an improvement in the clinical status of the wounds when compared to CG. These findings demonstrate the effectiveness and relevance of the employed technique. It can be easily incorporated as a routine procedure in hospitals without extra investment.

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ABSTRACT Objectives: To assess the efficacy of hydroxychloroquine in combination with azithromycin in terms of clinical and biochemical outcomes in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS), and to describe the occurrence of adverse events. Method: Retrospective comparative study, based in a quaternary private hospital in Rio de Janeiro, Brazil, involving 193 adult patients hospitalized for mild and moderate COVID-19 related ARSD, analyzing treatment efficacy based on clinical and biochemical outcomes. Results: The active group comprised 101 (52.3%) patients using hydroxychloroquine associated with azithromycin and the control group 92 (47.7%) patients who did not take these medications. Median age was 59 (47–70) in the active group and 65 (47−77) in the control group (p < 0.05). Patients in the control group had greater extent of pulmonary involvement on baseline chest CT scans (p < 0.05). All other baseline variables (BMI, comorbidities, previous use of medications and biochemical assessments) were similar between groups. In the medication group, 25% (25 out of 101) were admitted to the ICU, compared to 21% (19 out of 92) in the control group (p > 0.05). No difference in mortality, duration of non-invasive oxygen use or duration of hospitalization was seen between groups. The therapeutic regimen was well tolerated, with only eight (7.9%) patients presenting gastrointestinal symptoms and eight (7.9%) patients withdrawn treatment due to QTc prolongation. Conclusions: Patients treated with hydroxychloroquine combined with azithromycin and the control group had similar clinical outcomes. This therapeutic regimen was considered ineffective in hospitalized patients with mild to moderate COVID-19 related ARDS and was associated with few non-severe adverse events.

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ABSTRACT Objective: In recent years, the use of outpatient parenteral antimicrobial therapy (OPAT) has increased, resulting in the need to ensure its rational and adequate utilization. This article describes the implementation of an antimicrobial stewardship program in the OPAT setting by a Health Maintenance Organization (HMO) and its results. Method: An infectious disease (ID) physician made routine assessments of all home care parenteral antimicrobial requests from February to December 2019. Information on diagnosis, renal function, weight, previous antimicrobials, and microbiology were gathered during remote evaluations. Prescription changes recommended by the ID specialist were not mandatory, but implemented by the primary provider as accepted. Antibiotic consumption data was analyzed from January 2018 to December 2019. An active screening was conducted for treatment failures: two or more treatment course requirements, or death within 15 days of the evaluation were reexamined. Results: A total of 506 antimicrobial requests were assessed. The most frequent diagnoses were urinary tract infection, pneumonia, and orthopedic surgical site infection. Six percent of evaluations were not completed due to insufficient information and 12% were requests by the primary physician for initial antimicrobial guidance. Of the 416 completed prescriptions evaluations, 58% had suggested changes, including different antimicrobials (40%), treatment duration (25%), and route of administration (23%). There was an increase in use of teicoplanin and meropenem, and a decrease in ceftriaxone, ertapenem, cefepime, amikacin and daptomycin use. The HMO’s overall parenteral antimicrobial outpatient consumption, which had shown an upward trend over the previous year, decreased after program initiation. No major adverse results were detected in patients’ clinical outcomes; two treatment failures were detected and promptly corrected; no deaths attributed to antibiotic changes were detected. Conclusion: Outpatient antimicrobial stewardship, through remote assessment by an ID specialist, was effective and safe in the OPAT setting.

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ABSTRACT Introduction: Some COVID-19 patients have higher mortality and the responsible factors for this unfavorable outcome is still not well understood. Objective: To study the association between ferritin levels at admission, representing an inflammatory state, and hospital mortality in COVID-19 patients. Methods: From May through July 2020, SARS-CoV-2 positive patients with moderate to severe clinical symptoms were evaluated at admission, regarding clinical and laboratory data on renal and hepatic function, hematologic parameters, cytomegalovirus co-infection, and acute phase proteins. Results: A total of 97 patients were included; mean age = 59.9 ± 16.3 years, 58.8% male, 57.7% non-white, in-hospital mortality = 45.4%. Age, ferritin, C-reactive protein, serum albumin and creatinine were significantly associated with mortality. Ferritin showed area under the curve (AUC) of 0.79 (p < 0.001) for the cut-off of 1873.0 ng/mL, sensitivity of 68.4% and specificity of 79.3% in predicting in-hospital mortality. Age ≥60 years had an odds ratio (OR) of 10.5 (95% CI = 1.8–59.5; p = 0.008) and ferritin ≥1873.0 ng/mL had an OR of 6.0 (95% CI = 1.4–26.2; p = 0.016), both independently associated with mortality based on logistic regression analysis. Conclusion: The magnitude of inflammation present at admission of COVID-19 patients, represented by high ferritin levels, is independently predictive of in-hospital mortality.

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ABSTRACT SARS-CoV-2 has a high risk of outbreak in long-term skilled nursing facilities (SNF). Coronavirus disease (COVID-19) has high mortality rates among the elderly with chronic health conditions. Following identification of COVID-19 index case in a SNF, serial point-prevalence was implemented with reverse transcription–polymerase chain reaction (RT-PCR) and immunochromatographic assays. Active surveillance and early isolation of infected patients were implemented. Out of 23 SNF residents and 26 healthcare workers (HCW), 18 (78%) and 12 (46%) tested positive for SARS-CoV-2, respectively. High proportion (38%) of positive patients were asymptomatic and RT-PCR was positive up to six days before symptoms. Five (21.74%) residents were hospitalized with COVID-19, and 2 (9%) died; only 1 (4%) HCW needed to be hospitalized and no staff members died. Active surveillance helped COVID-19 control and management in a SNF. Testing symptomatic individuals only may fail to identify and isolate all persons contributing to transmission. In high-risk elderly, only symptoms screening may not be enough for outbreak control.

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ABSTRACT A retrospective cohort of 11,308 chronic hepatitis C infected patients treated with regimens that included Sofosbuvir (SOF), Daclatasvir (DCV), Simeprevir (SMV), or an association of Ombitasvir, Veruprevir/Ritonavir and Dasabuvir (3D) with or without Ribavirin (RBV) were assessed for sustained virologic response (SVR) or viral cure after a 12-week treatment. Logistic regression analyses were used to identify factors independently associated with positive response to direct-acting antivirals (DAA)-based therapies.Overall 57.1% were male; 48.3% self-identified as white; 78.3% were over 50 years old; 44.1% were from the Southeast region; 47.7% had genotype 1b; and 84.5% were treated for 12 weeks. The SVR rates with DAAs ranged from 87% to 100%. Genotypes 1 and 4 had higher SVR rates (96.3–100%), and genotypes 2 and 3 had SVR of 90.6–92.2%, respectively. Treatment durations of 12 and 24 weeks were associated with an average SVR of 95.0% and 95.9%, respectively. Females were half as likely (OR 0.5; 95% CI 0.4−0.6) to have a negative response to therapy compared to males, and those with genotypes 2 and 3 were one and half fold more likely (OR 1.5–2.2; 95 CI% 0.7–2.9; 1.2–3.6 and OR 2.7–2.8; 95% CI 2.0–3.8, respectively) to not have SVR compared to genotype 1. Patients in the age-range of 50–69 years old were 1.2-fold (OR 1.2; 95% CI 0.7–1.9) more likely to not have SVR compared to other age groups, although not statistically significant.This study is the first of this magnitude to be held in a Latin-American country with high SVR results, supported by a free-of-charge universal and public health system. The high performance found in this study gives support to the Brazilian public health policy decision of adopting DAA-based therapies as a strategy to eliminate HCV by 2030.

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ABSTRACT Introduction: Brazilian borreliosis (BB) disease is an infectious disease transmitted by ticks that mimics Lyme disease (LD) from the Northern Hemisphere. The BB clinical picture is characterized by a pathognomonic skin lesion (migratory erythema) and joint, neurological, cardiac and psychiatric symptoms. Innate and Th1/Th17 adaptive immunity seem to play an important role in the pathogenesis of Lyme disease. Objective: The aim of this study was to characterize the role of innate and Th1/Th17 adaptive immunity in BB patients with acute (<3 months) and convalescent (>3 months) disease. Methods: Fifty BB patients (28 with acute and 22 with convalescent disease) without treatment and 30 healthy subjects were evaluated. Levels of 20 cytokines or chemokines associated with innate and Th1/Th17 adaptive immunity were analyzed using Luminex (Millipore Corp., Billerica, MA). Results: Overall, BB patients had increased levels of IL-8 (6.29 vs 2.12 p = 0.002) and MIP-1α/CCL3 (5.20 vs 2.06, p = 0.030), associated with innate immunity, and MIP3B/CCL19 (Th1; 297.86 vs 212.41, p = 0.031) and IL-17A (Th17; 3.11 vs 2.20, p = 0.037), associated with adaptive immunity, compared with the levels of healthy controls. When comparing acute BB vs. convalescent BB subjects vs. healthy controls, IL-1β, IL-8 and MIP-1α/CCL3 (innate mediators) levels were highest in patients in the acute phase of disease (p < 0.05). TNF-α was associated with disseminated symptoms and with humoral reactivity against Borrelia burgdorferi. IL-10 was significantly correlated with IL-6 (r = 0.59, p = 0.003), IL-8 (r = 0.51, p < 0.001), MIP-1α/CCL3 (r = 0.42, p < 0.001) and MIP-3β/CCL19 (r = 0.40, p = 0.002) in all BB patients. Conclusions: This is the first study describing that innate and Th1/Th17 adaptive immunity play a crucial role in BB disease. Furthermore, innate mediators are particularly important in acute BB disease, and TNF-α is associated with evolution of BB symptoms.

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ABSTRACT This report shows the contribution of next-generation metagenomic sequencing (mNGS) as an alternative to challenging diagnostic infection in immunosuppressed individuals. Herein, we report three acute leukemia patients who developed severe invasive infections due to different etiologies: fungi, viruses, and protozoa. mNGS improved the diagnosis of the infections and provided the opportunity for adequate therapy. The mNGS is a hypothesis-free diagnostic platform, increasing potential in challenging diseases in hematological patients due to the extended diagnostic panel and the expedite access to the result.

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ABSTRACT Dolutegravir (DTG) is amongst the most prescribed antiretrovirals worldwide and is recommended as first line regimen in most HIV treatment guidelines. Its use, although infrequently, had been associated to an increased chance of neural tube defects (NTD) in Botswana, Africa. Herein we describe two cases of NTD in women who conceived while taking DTG as part of their antiretroviral treatment in the city of Porto Alegre, Brazil.

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ABSTRACT In the pandemic, rapid and accurate detection of SARS-CoV-2 is crucial in controlling the outbreak. Recent studies have shown a high detection rate using saliva/oral fluids as specimens for laboratory detection of the virus. We intended to evaluate the test performance of the Xpert Xpress SARS-CoV-2 cartridge assay in comparison to a conventional qRT-PCR testing, using saliva as biological specimen. Forty saliva samples from symptomatic participants were collected. Conventional qRT-PCR was performed for amplification of E and RdRp genes and the Xpert Xpress SARS-CoV-2 assay amplified E and N2 genes. In the conventional assay, the median cycle threshold value of the E gene was 34.9, and of the RdRp gene was 38.3. In the Xpert Xpress assay, the median cycle threshold value of the E gene was 29.7, and of the N2 gene was 31.6. These results can allow a broaden use of molecular tests for management of COVID-19 pandemic, especially in resources-limited settings.

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ABSTRACT The prevalence of sarcopenia in hospitalized people living with HIV is underdiagnosed, as assessment instruments are not always available. This study aimed to identify factors related to sarcopenia, correlating their anthropometric and clinical markers in hospitalized people living with HIV. This was an observational cross-sectional clinical study, carried out from September 2018 through October 2019. Handgrip strength, muscle mass index, calf circumference and gait speed test were evaluated in recruited patients within three days of hospital admission. The sample consisted in 44 patients, mostly men (66%), black (68%), young adults (41.65 ± 12.18 years) and immunodeficient (CD4 cell count 165 cells/mm3 [34.25–295.5]). Sarcopenia was present in 25% of the sample. Calf circumference showed a significant correlation with CD4 cell count and viral load (p < 0.05) while handgrip strength and gait speed test did not. Calf circumference > 31 cm and gait speed test > 0.8 m/s reduced the chance of sarcopenia by 60% (OR = 0.396 [−1.67 to −0.18]; p < 0.05) and 98% (OR = 0.02 [−8.16 to 0.13]; p < 0.05) respectively. Calf circumference > 31 cm and gait speed test > 0.8 m/s are associated with a reduced chance of sarcopenia in hospitalized HIV patients.